Nano-Ni(II)/Y Zeolite Catalyzed Synthesis of 2-Aryl- and 2-Alkyl Benzimidazoles Under Solvent-Free Conditions

Article abstract of DOI:10.1080/15533174.2015.1137020

Synthesis of some benzimidazole derivatives via condensation reaction of o-phenylenediamine derivatives with aromatic aldehydes or orthoesters under solvent-free conditions over nano-Ni(II)/Y zeolite as a heterogeneous catalyst is reported. Some advantages of this green method are easy purification, environmentally friendly conditions, low catalyst loadings, and nontoxic nature.

Full text of DOI:10.1080/15533174.2015.1137020

Synthesis and Reactivity in Inorganic, Metal-Organic, and
Nano-Metal Chemistry
ISSN: 1553-3174 (Print) 1553-3182 (Online) Journal homepage: http://www.tandfonline.com/loi/lsrt20
Nano-Ni(II)/Y zeolite catalyzed synthesis of 2-aryl-
and 2-alkyl benzimidazoles under solvent-free
conditions
A. Mobinikhaledi, M. Zendehdel, F. Goudarzi & G. Rezanejade Bardajee
To cite this article: A. Mobinikhaledi, M. Zendehdel, F. Goudarzi & G. Rezanejade Bardajee
(2016): Nano-Ni(II)/Y zeolite catalyzed synthesis of 2-aryl- and 2-alkyl benzimidazoles under
solvent-free conditions, Synthesis and Reactivity in Inorganic, Metal-Organic, and Nano-Metal
Chemistry, DOI: 10.1080/15533174.2015.1137020
To link to this article: http://dx.doi.org/10.1080/15533174.2015.1137020
Accepted author version posted online: 22
Feb 2016.
Submit your article to this journal
Article views: 3
View related articles
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=lsrt20
Download by: [La Trobe University]
Date: 27 February 2016, At: 17:12

ACCEPTED MANUSCRIPT
Nano-Ni(II)/Y zeolite catalyzed synthesis of 2-aryl- and 2-alkyl benzimidazoles under solvent-
free conditions
a,*
a
b
b
A. Mobinikhaledi , M. Zendehdel , F. Goudarzi , G. Rezanejade Bardajee
a
Department of Chemistry, Faculty of Science, Arak University, Arak 38156-8-8349, Iran
b
Department of Chemistry, Payame Noor University (PNU), P.O. Box 19395-4697, Tehran, Iran
*
Email: akbar_mobini@yahoo.com
Abstract
Synthesis of some benzimidazole derivatives via condensation reaction of o-phenylenediamine
derivatives with aromatic aldehydes or orthoesters under solvent-free conditions over nano-Ni(II)/Y
zeolite as a heterogeneous catalyst was reported. Some advantages of this green method are easy
purification, environmental friendly conditions, low catalyst loadings and non-toxic nature.
Keywords
Nano-Ni(II)/Y zeolite, o-phenylenediamine, benzimidazole, orthoesters, catalyst
1
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Introduction
Benzimidazole and its derivatives have found applications in design and discovery of new biological and
[1]
[2]
[3]
[4]
pharmaceutical compounds including antifungal,
anticancer,
antitumor , antibacterial,
[5]
[6]
[7]
[8]
antimicrobial, antihelmintic, antihypertensive and antiviral. Also, they have been used as
[9]
intermediates in organic and inorganic synthesis.
The most general methods for preparation of benzimidazoles is the condensation reaction of carboxylic
[10]
[11]
[12]
[13]
[14]
[15]
acids and its derivatives such as acid chlorides, nitriles, orthoesters, amides, esters and
[16]
recently aldehydes with o-phenylenediamine in the presence of different catalysts. The most of these
methods, which used for preparation of 2-aryl- and not for 2-alkyl benzimidazoles, are faced with
problems like requiring force reaction conditions, use of volatile or toxic organic solvents and use of
special reagent or catalyst.
Recently, special attentions have been focused on using zeolite as a solid acid catalyst in industrial and
organic synthesis due to their thermal stability, insolubility in organic solvents and low cost. It is worth
mentioning that the acidic sites of zeolite can catalyze organic reactions like condensation of diamines
and aldehydes.
In view of this report and also as a continuation of our works on the synthesis of
[17-20]
benzimidazoles,
we wish to report the synthesis of these materials in the presence of nano-Ni(II)/Y
zeolite as an efficient nano-catalyst via condensation reaction of orthoesters /aryl-aldehydes with o-
phenylenediamines.
Experimental
Materials and physical measurements:
2
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
All chemicals purchased from the Merck or Aldrich Company and used without further purification.
1
13
Melting points were measured in open capillary tubes and are uncorrected. H and C NMR spectra were
obtained in DMSO-d using Brucker spectrophotometer (300 MHz and 400 MHz). Chemical shifts (ppm)
6
were referenced to the internal standards tetramethylsilane (TMS). The IR spectral data were obtained
using a Galaxy FTIR 5000 spectrometer with KBr sample disk. The progress of reactions was monitored
by thin-layer chromatography (TLC) on silica gel F254 aluminium sheets (Merck). The scanning electron
microscopy (SEM) was done by Hitachi S 4160 apparatus.
Preparation of nano-Ni(II)/Y zeolite catalyst
[21]
Zeolite NaY was prepared and activated according to the literature. In a typical process, zeolite
(
2 g) and NiCl .6H O (2 mmol) were mechanically mixed, ground and heated using a microwave oven for
2
2
10-20 min with 900 Watt power. The temperature in the solid state ion-exchange was estimated around
700 C. The XRD pattern showed no metal salt remained and the solid state ion-exchange was
[22]
completed.
The prepared Ni(II)/Y zeolite was sonicated for 10 min in aceton solvent at room
temperature to obtain nano-sized catalyst.
Synthesis of 2-aryl benzimidazoles 3a-j
A mixture of o-phenylenediamine (1 mmol), aldehyde (1 mmol) and nano-Ni(II)/Y zeolite catalyst (0.02
g) was heated at 100°C for a desired time (Table 2) to give 2-aryl benzimidazole derivatives. The
progress of the reaction was investigated by tin-layer chromatography (TLC, eluent: n-hexane/ethyl
acetate 2:1). After completion of the reaction, hot ethanol was added (5-10 ml) and the catalyst was
separated by filtration. Then, ethanol evaporated and the resulted precipitate was recrystallized from
ethanol/water (1:2) to afford pure product.
Selected data:
3
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT

1
2
-Phenyl-1H-benzimidazole (3a): White solid; IR (KBr, cm ): 3435, 3113, 3063, 2943, 2868, 2791,
2542, 1770, 1682, 1587, 1485, 1410, 1363, 1302, 1273, 1246, 1201, 1134, 1003, 958, 887, 769, 746, 634

1 1
cm ; H NMR (DMSO-d , 300 MHz): δ (ppm) = 11.67 (br s, 1H), 7.73--8.67 (m, 9H); Anal. Calcd. for
6
C H N : C, 80.39; H, 5.19; N, 14.42%. Found: C, 80.50; H, 5.38; N, 14.56%.
1
3
10
2

1
2
-(4-Chlorophenyl)-1H-benzimidazole (3b): Light yellow solid; IR (KBr, cm ):3418, 3051, 2930,

1 1
2
849, 1614, 1541, 1491, 1429, 1321, 1273, 1224, 1172, 1091, 1012, 962, 829, 744, 615 cm ; H NMR
(
DMSO-d , 400 MHz): δ (ppm) = 13.00 (br s, 1H), 8.19 (d, J = 8.70 Hz, 2H), 7.63 (d, J = 8.70 Hz, 2H),
6
7
.49-7.24 (m, 2H), 7.26-7.19 (m, 2H); Anal. Calcd. for C H ClN : C, 68.28; H, 3.97; N, 12.25%. Found:
13 9 2
C, 68.51; H, 4.16; N, 12.43%.

1
2
-(2-Nitrophenyl)-1H-benzimidazole (3e): Yellow solid; IR (KBr, cm ): 3387, 3080, 2968, 2862, 1574,

1 1
1
527, 1446, 1415, 1379, 1348, 1278, 1224, 1078, 1010, 972, 854, 796, 721, 648 cm ; H NMR (DMSO-
d , 300 MHz): δ (ppm) = 13.09 (bs r, 1H), 7.84--8.56 (m, 8H); Anal. Calcd. for C H N O : C, 65.27; H,
6
13
9
3
2
3.79; N, 17.56%. Found: C, 65.11; H, 3.84; N, 17.67%.

1
2
1
1
1
-(4-Nitrophenyl)-1H-benzimidazole (3f): Yellow solid; IR (KBr, cm ): 3418, 3020, 2918, 2789, 1604,

1 1
514, 1435, 1340, 1292, 1226, 1101, 968, 854, 746, 711 cm ; H NMR (DMSO-d , 300 MHz): δ (ppm) =
6
3.34 (br s, 1H), 7.42 (s, 1H), 7.39-8.24 (m, 7H); Anal. Calcd. for C H N O : C, 65.27; H, 3.79; N,
1
3
9
3
2
7.56%. Found: C, 65.32; H, 3.74; N, 17.61%.

1
2
2
8
-(4-Methylphenyl)-1H-benzimidazole (3h): Light yellow solid; IR (KBr, cm ): 3346, 3084, 2949,
1
918, 1622, 1541, 1450, 1276, 972, 808, 704; H NMR (DMSO-d , 400 MHz): δ (ppm) = 12.83 (br s, 1H),
6
.06 (d, J = 8.40 Hz, 2H), 7.64-7.49 (m, 2H), 7.33 (d, J = 8.40 Hz, 2H), 7.19-7.18 (m, 2H), 2.37 (s, 3H);
Anal. Calcd. for C H N : C, 80.74; H, 5.81; N, 13.45%. Found: C, 81.04; H, 6.11; N, 13.15%.
14
12
2
4
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT

1
2
-Methyl-1H-Benzimidazole (6b): pale cream brown solid; IR (KBr, cm ): 3443, 3097, 3063, 2993,
1
2
914, 2791, 2679, 1622, 1556, 1450, 1417, 1386, 1271, 1219, 1028, 835, 734, 673, 617; H NMR
(
DMSO-d ): δ (ppm) = 12.23 (brs, 1H), 7.13-7.09 (m, 2H),7.48-7.44 (m, 2H), 2.49 (s, 3H);. Anal. Calcd.
6
for C H N : C, 72.70; H, 6.10; N, 21.20%. Found: C, 72.30; H, 5.79; N, 20.90%.
8
8
2

1
2
,5-Dimethyl-1H-Benzimidazole (6d): Dark brown solid; IR (KBr, cm ): 3300, 3013, 2914, 2858,
1
1
629, 1552, 1452, 1400, 1280, 1222, 1030, 858, 804, 667, 601; H NMR (DMSO-d , 400 MHz): δ (ppm)
6
=
12.02 (br s,1H), 7.28(d, J = 8.00 Hz, 1H), 7.23 (s, 1H), 6.92 (dd, J = 8.00 Hz, J = 1.20 Hz, 1H), 2.45
1 2
(
s, 3H), 2.38 (s, 3H); Anal. Calcd. for C H N : C, 73.94; H, 6.89; N, 19.16%. Found: C, 73.59; H, 6.54;
9 10 2
N, 18.83%.

1
5
-Nitro-1H-Benzimidazole (6e): Light yellow solid; IR (KBr, cm ): 3466, 3342, 3101, 2922, 2866,
1
2
739, 1790, 1655, 1591, 1465, 1408, 1302, 1242, 1182, 1105, 1066, 1022, 952, 898, 794, 740, 626; H
NMR (DMSO-d , 400 MHz): δ (ppm) = 13.02 (br s, 1H), 8.56 (s, 1H), 8.52 (d, J = 2.00 Hz, 1H), 8.13 (dd,
6
J = 8.80 Hz, J = 2.40 Hz, 1H), 7.78 (d, J = 8.80 Hz, 1H); Anal. Calcd. for C H N O : C, 51.54; H, 3.09;
1
2
7
5
3
2
N, 25.76%. Found: C, 51.84; H, 3.41; N, 25.46%.

1
2
2
1
8
-Methyl-5-nitro-1H-Benzimidazole (6f): Dark yellow solid; IR (KBr, cm ): 3485, 3317, 3107, 2978,
922, 2850, 2798, 2710, 2677, 1676, 1631, 1593, 1512, 1473, 1444, 1417, 1383, 1338, 1313, 1267, 1219,
1
124, 1064, 1026, 977, 879, 823, 738, 629;; H NMR (DMSO-d , 400 MHz): δ (ppm) = 12.85 (br s, 1H),
6
.38 (d, J = 2.00 Hz, 1H), 8.08 (dd, J = 8.80 Hz, J = 2.40 Hz, 1H), 7.66 (d, J = 8.80 Hz, 1H), 2.59
1
2
(
s,3H); Anal. Calcd. for C H N3O : C, 54.24; H, 3.98; N, 23.72%. Found: C, 54.01; H, 4.21; N, 23.59%.
8 7 2
Results and Discussion
The scanning electron microscopy (SEM) image of the nano-Ni(II)/Y particles, which was prepared in
solid state with microwave irradiation, is shown in Figure 1. The size of particles was mainly 80-100 nm.
5
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 1.
The FT-IR of the Ni(II)/Y zeolite nano-particles is presented in Figure 2. The intense band at ca.1060

1
cm is corresponded to the asymmetric stretching of Al--O--Si chain of zeolite. The symmetric stretching

1
and bending frequency bands of Al--O--Si framework of zeolite are observed at ca.790 and 451 cm ,
respectively. Transition metal /complexes encapsulated in the nano cages of zeolite did not show any
significant shift for functional groups stretching bond of zeolite. However, a new band appeared at 845

1
[23,24]
cm is related to Ni--O--T(T = Si or Al).
For comparison the XRD pattern of zeolite Y and nano
sized Ni(II)/Y zeolite particles is shown in Figures 3a and 3b, respectively. The results show that the
structure of zeolite does not collapse and six characteristic peaks appear at 2Ө of 30.1, 35.5, 43.1, 53.4,
57.0 and 62.6, which are marked by their indices ((220), (311), (400), (422), (511) and (440)) as shown in
[25,26]
Figure 3b.
To optimize the reaction conditions, the reaction of o-phenylenediamine (1 mmol) and benzaldehyde (1
mmol) was carried out using different amounts of nano-Ni(II)/Y zeolite catalyst, different solvents and
also under solvent-free conditions as a model reaction. A summary of obtained results is provided in
Table 1. At room temperature, the reaction rate was found to be slow and was increased with increase in
temperature. The best result was obtained when the reaction was carried out in the presence of 0.02 g of
nano-Ni(II)/Y zeolite under solvent-free conditions at 100 C (Table 1, entry 12). The catalyst and other
[27]
reaction conditions are safe in comparison to already reported results.
Encouraged by these results, we used this catalyst for synthesis of other benzimidazole derivatives under
solvent-free conditions using different aromatic aldehydes. Both electron-rich and electron-deficient
aldehydes worked well and leading to good yields of products 3a-j (Scheme 1). The results are given in
Table 2.
6
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
However, the aliphatic aldehydes such as formaldehyde or acetaldehyde were also examined under the
same conditions, but the corresponding products were isolated in trace amounts. Then, we attended to
synthesis some 2-alkyl benzimidazoles 6a-h by reaction of o-phenylenediamine derivatives with
orthoesters in the presence of nano-Ni(II)/Y particles at 60 C under the same conditions (Scheme 2,
Table 3). The possible mechanism for this reaction is shown in Scheme 3.
1
13
FT-IR, H and C NMR spectra data of 2-aryl and 2-alkyl benzimidazoles are similar and in consistent
1
with the expected structures. The H NMR spectra of benzimidazoles are simple and consist of a multiplet
and a broad singlet at downfield shift due to the resonance of aromatic protons and the NH group,
1
respectively. Also, the H NMR spectra of 2-alkyl benzimidazoles show an additional signal at highfiled
shift due to resonance of alkyl protons. The structure of compounds was also supported by IR spectra,

1
which included absorption bands at the regions 3259-3485 cm characteristic for the NH groups.
Conclusion
In conclusion, we have developed an efficient synthetic procedure for preparation of some benzimidazole
derivatives in the presence of nano-Ni(II)/Y zeolite catalyst. The short reaction time, high yield of
products, the absence of volatile organic solvents and non-toxic catalyst are some advantages of this green
method.
7
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
References
1. Bai, Y.B.; Zhang, A.L.; Tang, J.J.; Gao, J.M. Synthesis and antifungal activity of 2-
chloromethyl-1H-benzimidazole derivatives against phytopathogenic fungi in vitro. J. Agric.
Food Chem. 2013, 61, 2789-2795.
2. Husain, A.; Rashid, M.; Shaharyar, M.; Siddiqui, A.A.; Mishra, R. Benzimidazole clubbed
with triazolo-thiadiazoles and triazolo-thiadiazines: new anticancer agents.
Eur. J. Med. Chem. 2013, 62, 785-798.
3
. Sharma, A.; Luxami, V.; Paul, K. Synthesis, single crystal and antitumor activities of
benzimidazole-quinazoline hybrid. Bioorg. Med. Chem. Lett. 2013, 23, 3288-3294.
. Kumar, K.; Awasthi, D.; Lee, S.Y.; Cummings, J.E.; Knudson, S. E.; Slayden, R.A.; Ojima, I.
Benzimidazole-based antibacterial agents against Francisella tularensis. Bioorg. Med. Chem.
4
2013, 21, 3318-3326.
5. Seenaiah, D.; Ramachandra Reddy, P.; Mallikarjuna Reddy, G.; Padmaja, A.;
Padmavathi, V.; Siva Krishna, N. Synthesis, antimicrobial and cytotoxic activities of
pyrimidinyl benzoxazole, benzothiazole and benzimidazole. Eur. J. Med. Chem. 2014,
77, 1-7.
6. Ingle, R.G.; Magar, D.D. Heterocyclic chemistry of benzimidazoles and potential
activities of derivatives. Int. J. Drug. Res. Tech. 2011, 1, 26-32.
7. Kumar, J.R.; Jawahar, J.L.; Pathak, D.P. Synthesis of benzimidazole derivatives: As anti-hypertesive
agents. E-J. Chem. 2006, 3, 278-285.
8
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
8. Vitale, G.; Corona, P.; Loriga, M.; Carta, A.; Paglietti, G.; Giliberti, G.; Sanna, G.; Farci, P.;
Marongiu, M.E.; La Colla, P. 5-Acetyl-2-arylbenzimidazoles as antiviral agents. Part 4. Eur. J.
Med. Chem. 2012, 53, 83-97.
9
. Bai, Y.; Lu, J.; Shi, Z.; Yang, B. Synthesis of 2,15-hexadecanedione as a precursor of
muscone. Synlett. 2001, 12, 544-546.
0. Grimmett, M.R. Imidazole and Benzimidazole synthesis, 1997, Otago University, Academic
Press.
1. Ravi Kumar, K.; Satyanarayana, P.V.V.; Srinivasa Reddy, B. NaHSO -SiO -Promted solvent-free
1
1
4
2
synthesis of benzoxazoles, benzimidazoles and benzothiazole derivatives. J. Chem. 2012, 2013, Article
ID 151273.
1
2. Ansari, K.F.; Lal, C. Synthesis, physicochemical properties and antimicrobial activity of
some new benzimidazole derivatives. Eur. J. Med. Chem. 2009, 44, 4028-4033.
3. Karami, B.; Nikoseresht, S.; Khodabakhshi, S. Novel approach to benzimidazoles using Fe O4
1
3
nanoparticles as a magnetically recoverable catalyst. Chin. J. Catal. 2012, 33, 298-301.
14. Terashima, M.; Ishii, M. Synthesis. A facile synthesis of 2-substituted benzoxazoles. Synthesis. 1982,
6, 484-485.
15. Matsushita, H.; Lee, S.H.; Joung, M.; Clapham, B.; Janda, K.D. Smart cleavage reactions: The
synthesis of benzimidazoles and benzothiazoles from polymer-bound esters. Tetrahedron. Lett.
004, 45, 313-316.
2
9
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
16. Sammaiah, B.; Sumalatha, D.; Satyanarayana Reddy, G.S.; Rajeswari, M.; Sharada, L. N.
Cadmium chloride (CdCl ): a mild and efficient catalyst for the synthesis of benzimidazoles.
2
Int. J. Ind. Chem. 2012, 3, doi:10.1186/2228-5547-3-11.
17. Mobinikhaledi, A.; Hamta, A.; Kalhor, M.; Shariatzadeh, M. Simple synthesis and biological
evaluation of some benzimidazoles using sodium hexafluroaluminate, Na AlF , as an efficient catalyst.
3
6
Iran. J. Pharm. Res. 2014, 13, 95-101.
18. Zendehdel, M.; Mobinikhaledi, A.; Hasanvand Jamshidi, F. Conversion of acids to benzimidazoles
with transition metal/zeolites. J. Incl Phenom. Macro. 2007, 59, 41-44.
19. Mobinikhaledi, A.; Zendehdel, M.; Hasanvand Jamshidi, F. Zeolite-catalyzed synthesis of substituted
benzimidazoles under solvent- free condition and microwave irradiation. Synth. React. Inorg. Met-Org.
Chem. 2007, 37, 175-177.
20. Mobinikhaledi, A.; Foroughifar, N.; Zendehdel, M.; Jabbarpour, M. Conversion of aldehydes to
benzimidazoles using NaY zeolite. Synth. React. Inorg. Met-Org. Chem. 2008, 38, 390-393.
21. Breck, D.W.; Tonawanda, N.Y. Rystallene zeglite Y. 1964 Assigned to Union Carbide, Pat.
No.3130007, patented April 21.
2
1
2. Jacob, R.G.; Dutra, L.G.; Radatz, C.S.; S. Mendes, R.; Perin, G.; Lenardão, E. J. Synthesis of
,2-disubstituted benzimidazoles using SiO /ZnCl Tetrahedron. Lett. 2009, 50, 1495-1497.
2
2.
10
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
2
3. Zendehdel, M.; Kooti, M.; Amini, M.M. Dispersion and solid state ion exchange of VCl
CrCl ⋅6H O, MnCl ⋅4H O and CoCl ⋅6H O onto the surface of NaY zeolite using microwave
irradiation. J. Porous. Mat. 2005, 12, 143-149.
4. Kooti, M.; Zendehdel, M.; Amini, M. M. Esterification and intramolecular acylation reactions with
transition metal/zeolites. J. Incl Phenom Macro, 2002, 42, 265-268.
3
,
3
2
2
2
2
2
2
25. Zendehdel, M.; Cruciani, G.; Dondi, M.; Appraisal of microwave-assisted ion-exchange in mordenite
by crystal structure analysi. J. Porous. Mat, 2012, 19, 361-368.
2
6. Liu, J.; Yin, D.; Yin, D.; Fu, Z.; Li, Q.; Lu, G. ZnCl supported on NaY zeolite by solid-state
2
interaction under microwave irradiation and used as heterogeneous catalys
for high regioselective Diels--Alder reaction of myrcene and acrolein. J. Mol. Catal A. Chem, 2004, 209,
171-177.
27. Kalhor, M.; Khodaparast, N.; Zendehdel, M. Use of nano-CuY zeolite as an efficient and
eco-friendly nanocatalyst for facile synthesis of perimidine derivatives
Lett. Org. Chem. 2013, 10, 573-577.
2
8. Ravi Kumar, K.; Satyanarayana, P.V.V; Srinivasa Reddy, B. NaHSO -SiO promoted synthesis of
4 2
Benzimidazole derivatives. Arch. Appl. Sci. Res. 2012, 4, 1517-1521.
29. Boroujeni, K.P.; Zhianinasab, A.; Jafarinasab, M. Polystyrene-supported pyridinium chloroaluminate
ionic liquid as a new heterog eneous Lewis acid catalyst for selec-
tive synthesis of benzimidazoles. J. Serb. Chem. Soc. 2013, 78, 155-164.
11
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
30. Heravi, M.M.; Tajbakhsh, M.M.; Ahmadi, A.N.; Mohajerani, B. eolites: Efficient and eco-friendly
catalysts for the synthesis of benzimidazoles. Monatsh. Chem. 2006, 137, 175-179.
31. Sontakke, V.A.; Ghosh, S.; Lawande, P.P.; Chopade, B.A.; Shinde, V.S. A simple, efficient synthesis
of 2-aryl benzimidazoles using silica supported periodic Acid catalyst and evaluation of anticancer
activity. ISRN Org Chem. 2013; 2013: 453682. doi: 10.1155/2013/453682, Apr 24, 2013.
32. Naeimi, H.; Alishahi, N. Efficient, rapid and one pot synthesis of 2-substituted
benzimidazoles using the NaOH/I system as an oxidant under mild conditions
2
J. Chem. Res. 2013, 37, 208-209.
33. Khosravi, K.; Kazemi, S. Synthesis of 2-arylbenzimidazoles and 2-
arylbenzothiazoles in both room temperature and microwave condition catalyzed by
hexamethylenetetramine bromine comple. Chin. Chem. Lett. 2012, 23, 61-64.
34. Chen, G.F.; Dong, X.Y. Facile and selective synthesis of 2-substituted benzimidazoles catalyzed by
FeCl /Al O , E-J.Chem. 2012, 9, 289-293.
3
2
3
35. Padalkar, V.S.; Tathe, A.; Gupta, V.D.; Patil, V.S.; Phatangare, K.; Sekar, N. Synthesis and photo-
physical characteristics of ESIPT inspired 2-substituted benzimidazole, benzoxazole and benzothiazole
fluorescent derivatives. J. Fluoresc. 2012, 22, 311-322.
36. Bahrami, K.; Khodaei, M.M.; Nejati, A. Synthesis of 1,2-disubstituted benzimidazoles, 2-substituted
benzimidazoles and 2-substituted benzothiazoles in SDS micelles. Green Chem. 2010, 12, 1237.
37. Baltork, I.M.; Moghadama, M.; Tangestaninejad, S.; Mirkhania, V.; Zolfigol, M.A.; Hojatia, S.F.
Silica sulfuric acid catalyzed synthesis of benzoxazoles, benzimidazoles and oxazolo[4,5-b]pyridines
under heterogeneous and solvent-free conditions. J. Iran. Chem. Soc. 2008, 5, 65-70.
12
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
38. Zhang, Z.H.; Li, J.J.; Gao, Y.Z.; Liu, Y.H. Sinthesis of 2-substituted benzimidazoles by iodine-
mediated condensation of orthoesters with 1,2-phenylenediamines. J. Heterocyclic Chem. 2007, 44, 1509-
1
3
512.
9. Khaksar, S.; Heydari, A.; Tajbakhsh, M.; Vahdat, S.M. Lewis acid catalyst
free synthesis of benzimidazoles and formamidines in 1,1,1,3,3,3-hexafluoro-
2-propanol. J. Fluorine Chem. 2010, 131, 1377-1381.
40. De Luca, L.; Porcheddu, A. Microwave-assisted synthesis of polysubstituted
benzimidazoles by heterogeneous Pd-Catalyzed oxidative C--H activation of tertiary
amines. Eur. J. Org. Chem. 2011, 29, 5791-5795.
4
5
1. Rabiger, D.J.; Joullie, M.M. The ionization constants, and ultraviolet and infrared spectra of 4(7)- and
(6)-halogenated benzimidazoles. J. Chem. Soc. 1964, 915-1920.
42. Murray, M.; Ryan, A.J.; Little, P.J. Inhibition of rat hepatic microsomal aminopyrine N-
demethylase activity by benzimidazole derivatives. Quantitative structure-activity
relationships. J. Med. Chem. 1982, 25, 887-892.
13
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 1. The optimization of reaction conditions for synthesis of 2-aryl benzimidazole in the presence of nano-
Ni(II)/Y zeolite as a catalyst
Catalyst amount
g)
Temperature
a
Entry
Solvent
Time (min)
Yield (%)
(
(C)
1
2
3
4
5
6
7
8
9
0.01
0.01
25
50
60
60
60
50
60
60
60
60
80
100
120
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
15
15
15
10
10
10
38
42
53
68
10
6
trace
40
83
89
90
70
84
81
83
69
89
92
90
0.01
0.02
0.03
0.02
0.02
CH CN
3
0.02
DMF
0.02
DMSO
1
1
1
1
0
1
2
3
0.02
CHCl
3
0.02
solvent-free
solvent-free
solvent-free
0.02
0.02
4
a
Isolated yields
14
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 2. Synthesis of 2-aryl benzimidazole derivatives using nano-Ni(II)/Y catalyst at 100°C under solvent-free
conditions
Melting point (°C)
a
Time
Yield
(%)
Product 3
R
(
min)
Found
Reported
[
[
[
28]
a
H
6
92
289-291
2
89-291
29]
30]
b
4-Cl
4
20
6
95
91
95
90
92
86
89
87
92
290-292
219-221
273-275
209-211
308-310
218-221
267-269
190-192
228-229
288-290
218-219
274-276
212-214
310-312
222-224
266-269
c
2,4-Cl
2,6-Cl
[
31]
d
[
32]
e
2-NO
4-NO
2
2
7
[
29]
f
5
[
33]
g
4-OCH
3
15
6
[
34]
h
4-CH
3
[
35]
i
4-N(C
2
H
)
5
2
-2-OH
30
15
192
232
[
36]
j
4-N(CH )
3 2
a
Isolated yeilds
15
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Table 3. Synthesis of 2-alkyl benzimidazoles using Ni(II)/Y zeolite catalyst at 60°C under solvent-free conditions.
f
Time
Yield (%)
Melting point (°C)
Product 6
R
R'
R''
(
min)
Found
Reported
[
37]
a
H
H
H
CH
H
C
2
C
2
C
2
C
2
C
2
C
2
C
2
C
2
H
H
H
H
H
H
H
H
5
5
5
5
5
5
5
5
60
47
92
98
83
99
81
87
79
80
170-172
176-177
114-115
201-202
201-202
219-220
117-118
195-198
1
70-172
[
[
38]
38]
b
3
3
3
3
172-174
112-114
198-200
200-202
215-218
113-115
190-192
c
CH
CH
3
3
80
[
[
39]
38]
d
CH
H
46
e
NO
NO
Cl
2
2
118
87
[
[
[
40]
41]
42]
f
CH
H
g
122
85
h
Cl
CH
f
Isolated yeilds
16
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 1. The SEM image of nano-Ni(II)/Y zeolite particles
17
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 2. The FT-IR of the nano-Ni(II)/Y zeolite particles
18
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Figure 3. The comparison of the XRD of zeolite Y and Ni/Y zeolite
19
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Scheme 1.
Scheme 1. The synthetic pathway for synthesis of 2-aryl benzimidazoles
20
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
Scheme 2
Scheme 2. The synthetic pathway for synthesis of 2-alkyl benzimidazoles
21
ACCEPTED MANUSCRIPT

ACCEPTED MANUSCRIPT
NH2
NH2
R'
OR''
R
M-OZeolite
R''O
OR''
R' C OR''
R''O M-OZeolite
R''OH
OR''
R'C(OR'')
M-OZeolite
H OR''
N
R'
M-OZeolite
OR''
R
NH2
N
R'
R''OH
+
N
H
R
M-OZeolite
H
H
N
OR''
N
OR''
R'
R
N
R
NH2
R
H
M-OZeolite
R''O
R''OH
Scheme 3. The proposed mechanism for synthesis of 2-alkyl benzimidazoles in the presence of nano-
Ni(II)/Y particles
22
ACCEPTED MANUSCRIPT